title: Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion injury in the rat by an antioxidant action via inhibition of NADPH oxidase and iNOS expression.
abstract: OBJECTIVE
  This study was conducted to investigate the protective effects of CXC195, a tetramethylpyrazine analogue, in acute focal cerebral ischemia/reperfusion (I/R) injury in rats and to elucidate the potential mechanism.
  
  
  METHODS
  Middle cerebral artery occlusion for 2 h followed by reperfusion for 24 h was conducted in male Wistar rats and different doses of tetramethylpyrazine and CXC195 were intraperitoneally injected at 30 min after reperfusion.
  
  
  RESULTS
  Our results demonstrated that CXC195 at the dosage of 3 and 10 mg/kg significantly reduced the neurological deficit score and the infarct volume compared to the vehicle-treated group. In addition, CXC195 exhibited a protective effect against hippocampus neuronal cell death and significantly restored the brain ATP content. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capability (T-AOC), as well as production of malondialdehyde (MDA) and reactive oxygen species (ROS) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after I/R injury. Treatment with CXC195 significantly attenuated the decrease of SOD, GPx and T-AOC activities and inhibited the elevation of MDA content and ROS generation. Furthermore, CXC195 prevented the upregulation of the NADPH oxidase (NOX) 2 and NOX4, and reduced inducible nitric oxide synthase (iNOS) induction and production of nitric oxide induced by I/R.
  
  
  CONCLUSIONS
  These results suggest that CXC195 has a neuroprotective effect in transient focal ischemia, which is most likely due to its antioxidant activity by inhibiting NOX and iNOS expression.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.forename: Senpeng
authors.initials: S
authors.lastname: Li
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; C552200:CXC 195; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; D010879:Piperazines; D011719:Pyrazines; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat